PEDIGREE: Prenatal Environmental Determinants of InterGenerational Risk

PEDIGREE：代际风险的产前环境决定因素

基本信息

批准号：
8137817
负责人：
BARBARA A COHN
金额：
$ 38.19万
依托单位：
PUBLIC HEALTH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-03 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8137817
关键词：
Address Adult Adult Children Advocate Age Age at Menarche Animal Experiments Anthropometry Archives Biological Assay Birth Blood specimen Breast Chemicals Child Development Child health care Childhood Chlorinated Hydrocarbons Collaborations DNA Methylation Data Data Analyses Daughter Development Diagnosis Ductal Education Endocrine Endocrine disruption Enrollment Environmental Exposure Epidemiology Epigenetic Process Exposure to Family Family history of Female Fetus Funding Future Generations Growth Health Hormones Human Income Individual Infant Lactation Life Mammographic Density Mammography Maternal Age Maternal Exposure Measures Mediator of activation protein Modeling Mothers Occupations Outcome Participant Paternal Age Pathology Pathway interactions Perinatal Exposure Pharmaceutical Preparations Polychlorinated Biphenyls Population Study Predisposition Pregnancy Preparation Principal Investigator Proxy Publishing Race Recording of previous events Records Reproductive History Research Research Design Research Personnel Resources Risk Risk Factors Role Sample Size Sampling Serum Specimen Testing Tumor Markers Tumor Tissue Uterus Variant Weight Gain Woman Work anticancer research base breast density cancer risk carcinogenesis case control cohort critical period empowered epidemiologic data exposed human population follow-up human population study in utero interest intergenerational malignant breast neoplasm member novel offspring organochlorine exposure organochlorine pesticide prenatal prenatal environmental exposure prenatal exposure steroid hormone success

项目摘要

DESCRIPTION (provided by applicant): The investigators propose a unique study of human exposure to organchlorines during two critical windows of exposure for the breast: 1) pregnancy when preparation for lactation places the breast at risk for carcinogenesis in the mother and 2) the prenatal period when breast differentiation places the breast at risk for carcinogenesis in the daughter. There are few human studies where exposure to endocrine active compounds during these critical periods can be measured directly in relation to subsequent breast cancer risk. The proposed research addresses this gap and represents a novel and unique opportunity, efficiently using an existing cohort that spans two generations. The investigators will also develop the capacity for cohort members to participate as full research partners, enhancing the relevance and success of continuing breast cancer research in this unique study population. This study is made possible by a 50-year follow-up of the Child Health and Development Studies Pregnancy Cohort (CHDS). Maternal pregnancy serum samples were collected during peak exposure to organochlorine pesticides and polychlorinated biphenyls in the 1960's, prior to the ban on these chemicals. The proposed research funds organochlorine serum assays for recently diagnosed cases of breast cancer in mothers to extend the sample size for a prior published study of maternal breast cancer, collects 200 mammograms for daughters of mothers who have been diagnosed with breast cancer, assays 400 adult daughter specimens for DNA methylation, supports new data analysis to 1) test a novel hypothesis that maternal exposure during a critical window (prior to age 14) increases susceptibility of the fetus to the effects of environmental exposures in the womb; 2) test a well accepted hypothesis where data have not heretofore been available; that daughters of women who developed breast cancer are more susceptible to environmental exposures in the womb; and 3) examine the role of pregnancy hormone exposures in explaining observed organochlorine associations with breast cancer in mothers and age at menarche, mammographic density and DNA methylation of their daughters.

描述（由申请人提供）：研究人员提出了一项独特的研究，研究人类在乳房暴露的两个关键窗口期间接触有机氯：1）怀孕期间，为哺乳做准备，使母亲的乳房面临致癌风险；2）产前乳房分化使女儿的乳房面临致癌风险的时期。很少有人类研究可以直接测量这些关键时期接触内分泌活性化合物与随后患乳腺癌风险的关系。拟议的研究解决了这一差距，并代表了一个新颖而独特的机会，有效地利用了跨越两代人的现有群体。研究人员还将培养队列成员作为全面研究合作伙伴参与的能力，从而提高这一独特研究人群中持续乳腺癌研究的相关性和成功率。这项研究是通过对儿童健康与发育研究妊娠队列 (CHDS) 50 年的跟踪调查而得以实现的。孕产妇妊娠血清样本是在 20 世纪 60 年代有机氯农药和多氯联苯被禁止之前的接触高峰期收集的。拟议的研究资助对最近诊断出的母亲乳腺癌病例进行有机氯血清测定，以扩大先前发表的母体乳腺癌研究的样本量，为已被诊断患有乳腺癌的母亲的女儿收集 200 份乳房 X 光检查，对 400 名成年女儿进行测定DNA 甲基化样本，支持新的数据分析，以 1) 测试一个新的假设，即母亲在关键窗口期（14 岁之前）的暴露会增加胎儿对环境影响的易感性在子宫内的暴露； 2）测试迄今为止尚未获得数据的广为接受的假设；患有乳腺癌的妇女的女儿在子宫内更容易受到环境暴露的影响； 3) 研究妊娠激素暴露在解释观察到的有机氯与母亲乳腺癌及其女儿初潮年龄、乳房 X 光密度和 DNA 甲基化之间的关系方面的作用。